Abstract:
:Porcine reproductive and respiratory syndrome virus (PRRSV) infection eliminates production of type I interferons (IFNs) in host cells, which triggers an antiviral immune response through the induction of downstream IFN-stimulated genes (ISGs), thus escaping the fate of host-mediated clearance. The IFN-induced transmembrane 3 (IFITM3) has recently been identified as an ISG and plays a pivotal role against enveloped RNA viruses by restricting cell entry. However, the role of IFITM3 in PRRSV replication is unknown. The present study demonstrated that overexpression of IFITM3 suppresses PRRSV replication, while silencing of endogenous IFITM3 prominently promoted PRRSV replication. Additionally, it was shown that IFITM3 undergoes S-palmitoylation and ubiquitination modification, and both posttranslational modifications contribute to the anti-PRRSV activity of IFITM3. Further study showed that PRRSV particles are transported into endosomes and then into lysosomes during the early stages of infection, and confocal microscopy results revealed that PRRSV particles are transported to IFITM3-positive cellular vesicles. By using a single virus particle fluorescent labeling technique, we confirmed that IFITM3 can restrict PRRSV membrane fusion by inducing accumulation of cholesterol in cellular vesicles. Additionally, we found that both endogenous and exogenous IFITM3 are incorporated into newly producing PRRS virions and diminish viral intrinsic infectivity. By using cell coculture systems, we found that IFITM3 effectively restricted PRRSV intercellular transmission, which may have been caused by disrupted membrane fusion and reduced viral infectivity. In conclusion, our results demonstrate, for the first time, that swine IFITM3 interferes with the life cycle of PRRSV, and possibly other enveloped arteritis viruses, at multiple steps.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS), which is caused by PRRS virus (PRRSV), is of great economic significance to the swine industry. Due to the complicated immune escape mechanisms of PRRSV, there are no effective vaccines or therapeutic drugs currently available against PRRS. Identification of cellular factors and underlying mechanisms that establish an effective antiviral state against PRRSV can provide unique strategies for developing antiviral vaccines or drugs. As an interferon (IFN)-stimulated gene, the role of IFN-induced transmembrane 3 (IFITM3) in PRRSV infection has not been reported as of yet. In the present study, it was shown that IFITM3 can exert a potent anti-PRRSV effect, and PRRS virions are trafficked to IFITM3-containing cell vesicles, where viral membrane fusion is impaired by cholesterol accumulation that is induced by IFITM3. Additionally, both endogenous and exogenous IFITM3 are incorporated into newly assembled progeny virions, and this decreased their intrinsic infectivity.
journal_name
J Viroljournal_title
Journal of virologyauthors
Zhang A,Duan H,Zhao H,Liao H,Du Y,Li L,Jiang D,Wan B,Wu Y,Ji P,Zhou EM,Zhang Gdoi
10.1128/JVI.01350-20subject
Has Abstractpub_date
2020-11-23 00:00:00issue
24eissn
0022-538Xissn
1098-5514pii
JVI.01350-20journal_volume
94pub_type
杂志文章abstract::Several C/EBP binding sites within the Rous sarcoma virus (RSV) long terminal repeat (LTR) and gag enhancers were mutated, and the effect of these mutations on viral gene expression was assessed. Minimal site-specific mutations in each of three adjacent C/EBP binding sites in the LTR reduced steady-state viral RNA lev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.5.2862-2870.1993
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abstract::A detailed analysis of the expression of the bacterial chloramphenicol acetyltransferase gene controlled by the herpes simplex virus major capsid protein (VP5) promoter showed that this promoter can be functionally separated into an 80-base core region, which has the minimal information required to serve as a pol II p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.460-469.1986
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.23.1.167-176.1977
更新日期:1977-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.3.1128-1139.1977
更新日期:1977-03-01 00:00:00
abstract::Murine gammaherpesvirus 68 (MHV68) is a gammaherpesvirus that was first isolated from murid rodents. MHV68 establishes a latent infection in the spleen and other lymphoid organs. Several gammaherpesviruses, including herpesvirus saimiri, human herpesvirus 8, and MHV68, encode proteins with extensive homology to the D-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.15.7016-7023.2000
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.1.46-59.1981
更新日期:1981-07-01 00:00:00
abstract::The regulatory proteins Nef, Rev, and Tat of human immunodeficiency virus type 1 (HIV-1) are attractive targets for vaccine development, since induction of effective immune responses targeting these early proteins may best control virus replication. Here we investigated whether vaccination with biologically active Tat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.8.3800-3809.2002
更新日期:2002-04-01 00:00:00
abstract::The p24 protein, one of the three proteins implicated in local movement of potato virus X (PVX), was expressed in transgenic tobacco plants (Nicotiana tabacum Xanthi D8 NN). Plants with the highest level of p24 accumulation exhibited a stunted and slightly chlorotic phenotype. These transgenic plants facilitate the ce...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.1.731-738.1998
更新日期:1998-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1394-1402.1998
更新日期:1998-02-01 00:00:00
abstract::Yaba tumor poxvirus deoxyribonucleic acid (DNA) has a density of 1.6905 in CsCl and its T(m) value in 0.015 m citrate in saline is 82.3. The guanine plus cytosine content estimated from these properties was taken to be 32.5 +/- 0.5%, a value 2 to 3% less than for DNA from other poxviruses reported to date. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.2.114-118.1969
更新日期:1969-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.22.14355-14370.2005
更新日期:2005-11-01 00:00:00
abstract::Alternative splicing of adeno-associated virus type 2 (AAV2) P19-generated pre-mRNAs generates the small Rep proteins Rep52 and Rep40, which differ in their carboxyl termini. Both proteins are required for optimal packaging of AAV2 genomes. AAV5 Rep-encoding P19-generated transcripts are primarily polyadenylated withi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01961-09
更新日期:2010-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05869-11
更新日期:2011-12-01 00:00:00
abstract::The ribonucleic acid (RNA) of murine leukemia virus (MLV) Rauscher strain was observed by the aid of electron microscopy with the use of the protein monolayer technique. RNA was observed directly after release from virus particles or after isolation by sedimentation in sucrose density gradients. Molecules were found i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.4.4.460-474.1969
更新日期:1969-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.7.3141-3148.2000
更新日期:2000-04-01 00:00:00
abstract::Nidoviruses (arteriviruses, coronaviruses, and roniviruses) are a phylogenetically compact but diverse group of positive-strand RNA viruses that includes important human and animal pathogens. Nidovirus RNA synthesis is mediated by a cytoplasmic membrane-associated replication/transcription complex that includes up to ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00261-09
更新日期:2009-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.7.2198-2207.1987
更新日期:1987-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.17.7864-7871.2001
更新日期:2001-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.1.663-666.1996
更新日期:1996-01-01 00:00:00
abstract::Biological and genetic variability is a prominent feature of human immunodeficiency virus (HIV) strains, especially in tropism, syncytium formation, and replicative capacity. To determine whether there were variable host cell effects on HIV replication in monocytes, three different strains of low-passage-number monocy...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.11.7792-7803.1996
更新日期:1996-11-01 00:00:00
abstract::The question of whether any mammalian cells are able to mount an effective RNA interference-mediated antiviral innate immune response has remained highly controversial. In this Gem, I review recent data addressing this important issue and propose a testable hypothesis that can explain many of the apparently contradict...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.01179-14
更新日期:2014-11-01 00:00:00
abstract::The nucleic acids of influenza A, B, and C viruses were compared. Susceptibility to nucleases demonstrates that influenza C virus, just as influenza A and B viruses, possesses single-stranded RNA as its genome. The base compositions of the RNAs of influenza A, B, and influenza C virus are almost identical and comparat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.2.738-744.1976
更新日期:1976-05-01 00:00:00
abstract::TMC114, a newly designed human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is extremely potent against both wild-type (wt) and multidrug-resistant (MDR) viruses in vitro as well as in vivo. Although chemically similar to amprenavir (APV), the potency of TMC114 is substantially greater. To examine the bas...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.21.12012-12021.2004
更新日期:2004-11-01 00:00:00
abstract::Cylindrical projections surrounding the fivefold-symmetry axes in minute virus of mice (MVM) harbor central pores that penetrate through the virion shell. In newly released DNA-containing particles, these pores contain residues 28 to 38 belonging to a single copy of VP2, disposed so that its extreme N-terminal domain ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.1.161-171.2006
更新日期:2006-01-01 00:00:00
abstract::Ebola virus (EBOV) causes severe hemorrhagic fever, for which therapeutic options are not available. Preventing the entry of EBOV into host cells is an attractive antiviral strategy, which has been validated for HIV by the FDA approval of the anti-HIV drug enfuvirtide. To identify inhibitors of EBOV entry, the EBOV en...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01456-10
更新日期:2011-04-01 00:00:00
abstract::A number of options are available to modify and improve DNA vaccines. An interesting approach to improve DNA vaccines is to fuse bioactive domains, like cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), to an antigen. Such fusion antigens are expressed in vivo and directed to immune cells by the specific bioactive...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.10.6368-6376.2005
更新日期:2005-05-01 00:00:00
abstract::The region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region. DNase I protection analysis with human cell nuclear extracts demonstrated multiple protein binding sites in this region of the viral genome (P. Gha...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9039-9052.1999
更新日期:1999-11-01 00:00:00
abstract::The family Geminiviridae comprises seven genera differentiated by genome organization, sequence similarity, and insect vector. Capulavirus, an eighth genus, has been proposed to accommodate two newly discovered highly divergent geminiviruses that presently have no known vector. Alfalfa leaf curl virus, identified here...
journal_title:Journal of virology
pub_type: 杂志文章,评审
doi:10.1128/JVI.00453-15
更新日期:2015-09-01 00:00:00